Fibrin is a major component of blood clots. Fibrin is a fibrillar protein derived from the soluble plasma protein fibrinogen. During the clotting cascade the enzyme thrombin cleaves fibrinopeptides on fibrinogen resulting in an end-to-end polymerization to give the polymer fibrin. The transglutaminase Factor XIII further stabilizes the fibrin mesh by crosslinking the fibrin fibrils. Fibrin is found in all thrombi: fresh thrombus, old thrombus; thrombus in the venous system, arterial system, and cardiac chambers. In this respect fibrin is different from activated platelets which are found mainly in fresh thrombi in the arterial system. Besides thrombus, fibrin is often associated with solid tumors, and is found in the tumor stroma. Fibrin is often associated with complex atherosclerotic plaque where it is believed to be present as a result of plaque rupture or fissure and subsequent healing.
Fibrin is a broadly useful target for imaging. For instance, since fibrin is found in thrombus but not in the circulating blood, a fibrin-targeted imaging would be expected to have high specificity for disease. The concentration of circulating fibrinogen is on the order of 1.5-4.0 g/L (4-12 μM), and one expects similar and higher levels of fibrin in thrombus. High concentrations of fibrin, coupled with its presence in all types of thrombi suggest that a fibrin-targeted imaging would have high sensitivity for disease as well.
Because of the perceived sensitivity and specificity for disease, and the relevance of fibrin in thromboembolic disease, cancer, and vulnerable atherosclerotic plaque, there have been several efforts to develop fibrin-specific imaging probes. This large body of scientific and patent literature speaks to the still unmet medical need of imaging fibrin in order to detect, diagnose, or monitor therapy for thromboembolic diseases and cancer. Despite the innovative approaches to imaging fibrin, there remains room for improvement.